This application claims the benefit of U.S. Provisional Application No. 60/000,435, filed Jun. 23, 1995.
Nisin is a bacteriocin, an antimicrobial substance produced by a food grade organism and is a member of a group of similar substances referred to as lantibiotics (or lanthocins herein) and which, among others, include subtilin, epidermin, gallidermin, pep 5, cinnamycin, duramycin and ancovenin.
Nisin is produced by Lactococcus lactis subsp. lactis belonging to the Lancefield serological group. N Mattick, A. T. R. and A. Hirsch, 1947 Lancet. 2, 5!. Nisin is a peptide comprised of 34 amino acid residues and contains five ring structures cross linked by thioether bridges that form lanthionine or .beta.-methyllanthionine. These thioethers result from the condensation of cysteine sulfhydryl groups with dehydro side chains formed from either serine or threonine residues as a result of posttranslational modifications of a nisin precursor peptide.
It has been reported that nisin acts as a cationic surface active agent and that its activity can be neutralized by anionic detergents Ramseier, H. R. 1960 Arch. Mikrobiol, 37, 57!, and at a molecular level that nisin acts at the cytoplasmic membrane and inhibits peptidoglycan biosynthesis Reisinger et al. 1980 Arch. Microbiol. 127, 187 !. The action of nisin against vegetative bacteria is most likely the result of voltage dependent depolarization of the plasma membrane following insertion of the peptide into the lipid bilayer, possibly through the interaction of adjacent nisin molecules to form a transient pore or channel. The molecular properties of nisin and the mechanism of its biosynthesis have been the subject of extensive recent reviews Jung, G. and H. -G. Sahl 1991 Nisin and Novel Lantibiotics ESCOM Science Publishers, Leiden!.
Nisin is considered to have a narrow spectrum of activity and generally is only active against certain Gram positive bacteria, except when combined with a chelating agent when nisin is surprisingly active against Gram negative bacteria and exhibits enhanced activity against Gram positive bacteria (U.S. Pat. Nos. 5,135,910; 5,217,950; and 5,260,271 to Blackburn, et al.). Nisin has been used as an antimicrobial food preservative and is accepted as safe by JEFCA and various national authorities regulating the use of food additives including those of the USA, UK and EEC.